Scientists finally clone human embryos

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For some time, scientists have been able to craft precise genetic copies of many creatures. Whether they are animals, or single cells, they are similarly referred to as clones. For various technical and perceived ethical reasons, the procedures involved have been difficult to replicate for humans. A new paper published in the journal Cell shares the work of a group of researchers in Oregon who have grown a human clone — at least up to a couple hundred cells. Given the nature of some of the manipulations involved, and the constitution of the resultant cell mass, it is not realistic to imagine that the amalgam they created would ever develop much beyond the stage they present. They therefore do not call their achievement an “embryo” as such. The intended use of this finely-tuned cell bank is rather to provide personalized stem cell resources to those who have already wrought for themselves a conscious form, and wish to forestall its untimely dissolution.

The usual technique for cloning an animal, if any can be said to be usual, typically involves a procedure called somatic cell nuclear transfer (SCNT). In this procedure, the nucleus of the cell to be cloned is injected into an unfertilized egg. Frequently the cell used is a generic cell type called a fibroblast. These cells make various connective tissue factors and can be readily obtained from the skin. Previously, the cell mass arising from humans cloned in this way usually fails to thrive by around the 8 or 16 cell stage. The Oregon researchers were able to firm-up both the ingredients and procedures of one particular recipe that showed promise in extending that limit. Key elements involved were to preserve parts of the cytoplasmic material that normally surrounds the nucleus of the host egg, so that critical skeletal structure of the egg is maintained in the proper form. This spindle apparatus, and other, more mobile molecular players that manipulate it, are essential to positioning subcellular components for the next division cycle.

Rather than injecting the donor nucleus, the donor cell was induced to fuse with the egg by passage of weak electric currents. In a rather shocking admission of lack of specificity still left in the field, the authors wondered if the electric current itself could also have some Frankenstein-like activation effect on the egg. Another surprising twist is that one adjuvant (think of it as a pharmaceutical catalyst) mixed into the maturation cocktail was good old caffeine (1.25 mM to be exact). A liter sized tub of pure caffeine is actually not an uncommon sight on the shelves of many molecular biology labs. It has roles in inhibiting the activities of various cellular components, like for example, proteins called phosphatases. If embryos constructed this way in the future are eventually brought to term, the grown child is probably going to get one heck of a reverse-withdrawal rush from their first cup of java.

It is of interest to note that while the maternal nuclear DNA is never incorporated into the cloned genome here, there is another critical source of host cell genetic material present — the mitochondria. In sperm-fertilized embryos, the egg quickly dispatches all the male mitochondria as soon as she gets the nuclear material. The male mitochondria are metabolically spent by the time they reach the egg and are loaded with the free-radical byproducts of their focused efforts. Following various assaults, they wither up like Chinook salmon after a long upstream journey, and their radical-damaged DNA is thereby eliminated from polluting the egg’s comparatively well-preserved mitochondrial pool. The researchers did not fully characterize mitochondrial fate in the present study. Although they looked for donor mitochondria, they found none, suggesting that only the maternal mitochondria persisted in the cloned cells.

The Cell paper really only touches on many of the elements involved in the successful cloning. There are many differences between the research done today, and that done over a decade ago when the first sheep, Dolly, was cloned. One difference is the availability of large gene arrays to rapidly profile the expression of hundreds of genes. These profiles can be taken at various points to see which proteins get made, and how they contribute to development. The full description for cloning a human obviously does not fit inside the methods section of any single paper. Not that any such procedure should be made too easy for anybody to follow; some more ordered algorithmic presentation would be desirable to have within the field. Perhaps something reminiscent of the engineer’s CAD model history would make these procedures a little more repeatable when translated between labs. Either way, this is an incredible advance for our species.

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